Bayer today announced positive data on its investigational compound copanlisib, an intravenous pan-Class I phosphatidylinositol-3-kinase (PI3K) inhibitor with predominant inhibitory activity against PI3K-α and PI3K-δ isoforms. The Phase II CHRONOS-1 trial, an open-label, single-arm study evaluating patients with relapsed or refractory indolent non-Hodgkin's lymphoma (iNHL), met its primary endpoint of a pre-specified objective response rate (ORR). The results across all patient groups show an ORR of 59.2%, with a 12% complete response (CR) rate and a median duration of response (DOR) of more than 98 weeks, or 687 days (range 0-687). These data will be presented at the American Association for Cancer Research (AACR) 2017 Annual Meeting in Washington, D.C. in the Novel Agent and Intervention Clinical Trials session on April 4, 2017 from 3:05 p.m. - 3:20 p.m. EDT.
"Based on the National Comprehensive Cancer Network (NCCN) guidelines, inhibition of the PI3K pathway has been shown to be a promising therapeutic pathway in treating indolent lymphomas, like follicular lymphoma," said Martin Dreyling, Professor of Medicine at the University of Munich Hospital in Grosshadern.
The full analysis set comprised 142 patients, of which 141 patients had iNHL. At the time of analysis, median duration of treatment was 22 weeks and 46 patients remained on treatment. In the follicular lymphoma (FL) subset of CHRONOS-1 (n=104), copanlisib treatment resulted in an ORR of 58.7%, including a CR of 14.4% and a median DOR of more than 52 weeks, or 370 days (range 0-687). The safety was generally consistent with previously published data on copanlisib. The most common treatment-related adverse events were transient hyperglycemia (all grades: 49%/Grade ≥3: 40%), which did not show severity above Grade 4, and hypertension (all grades: 29%/Grade ≥3: 23%), which did not show severity above Grade 3.
"NHL is the tenth most common cancer worldwide and one of the most common cancers in the U.S.1,2 Despite treatment advances, most indolent NHL patients relapse after, or are refractory to, current therapies," said Robert LaCaze, Executive Vice President and Head of the Oncology Strategic Business Unit at Bayer. "The positive results from CHRONOS-1 are an important milestone and reflect the potential clinical utility of copanlisib in addressing the unmet medical need in patients with malignant lymphoma."
Other copanlisib data to be presented at AACR 2017 include preclinical analysis of copanlisib activity in B-cell lymphomas as a single agent or in combination with conventional and targeted agents and a study on the binding affinity of copanlisib.
Bayer is in discussion with the U.S. Food and Drug Administration (FDA) with respect to a New Drug Application (NDA), seeking accelerated approval of copanlisib for the treatment of relapsed or refractory FL who have received at least two prior therapies. The company has been granted Fast Track Designation by the FDA for copanlisib for this indication. Fast Track is a program designed to facilitate the development, and expedite the review of drugs to address unmet medical need in the treatment of a serious or life-threatening condition.
Copanlisib was also granted Orphan Drug Designation (ODD) by the FDA Office of Orphan Products Development in the U.S. in February 2015 for the treatment of FL and in February 2017 for the treatment of splenic, nodal, and extranodal subtypes of marginal zone lymphoma (MZL). The ODD program provides orphan status to drugs and biologics which are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases and disorders. The FDA regards any disease that affects less than 200,000 patients in the U.S. as rare.